CN116801932A

CN116801932A - Administration balloon catheter

Info

Publication number: CN116801932A
Application number: CN202180038866.XA
Authority: CN
Inventors: 骆静南; 李博怀摩西
Original assignee: Junde Singapore Laboratories Ltd
Current assignee: Xiamen Junde Medical Technology Co ltd
Priority date: 2020-11-17
Filing date: 2021-11-16
Publication date: 2023-09-22
Also published as: US20230381469A1; EP4247467A1; WO2022108528A1

Abstract

The invention provides a drug infusion catheter (100) comprising an axially extending elongate member (101), an inflatable balloon (121) and two or more cannulas (122), each cannula having a retractable needle (123) disposed therein. When the balloon (121) is inflated, the distal portion of the sleeve (122) does not exceed the outermost diameter of the inflatable balloon (121). The drug infusion catheter (100) facilitates delivery of a drug to a lumen of a body vessel or tissue surrounding a blood vessel.

Description

Administration balloon catheter

Technical Field

The present invention relates to a device, i.e. a catheter, e.g. a rapid exchange catheter or an Over the wire catheter, for delivering a drug into a body, in particular into a physiological cavity or tissue surrounding a blood vessel.

Background

The delivery of drugs into the body can be accomplished in a variety of ways including, for example, oral, submucosal, parenteral, and transdermal administration. However, these methods are often affected by nonspecific delivery, which leads to potential off-target side effects. Since the administration efficiency is critical in the treatment of diseases, concentrated administration can improve the therapeutic effect and reduce side effects.

A technique of almost completely delivering a drug to a desired site is called smart drug delivery. The intelligent administration can improve the bioavailability of the medicine at the disease site, thereby reducing the administration frequency and maximally reducing the side effects generated by systemic administration. Smart dosing can be achieved by a number of possible methods, such as using nanoparticle carriers with strong affinity for specific proteins to control the final location of the therapeutic agent. However, one disadvantage of this approach is that the target site requires sufficiently distinct nanoparticle carriers to be able to distinguish the target site from other locations. This means that the method is not applicable in all cases.

Direct injection of therapeutic agents into the treatment area is one of the simplest methods of controlling therapeutic agent delivery. However, this approach becomes difficult when the target site is difficult to reach. At the time of injection, the needle is typically inserted from outside the body, penetrating the skin and other tissue, until the tip of the needle reaches the target site. The therapeutic agent is then injected directly into the target with a needle. The main limiting factor of this approach is whether the needle can reach the target site. This approach does not allow access to areas such as areas covered by bone. Another disadvantage of this method is that the needle must pass through most of the patient's tissue to reach the target site, and thus it is difficult to achieve a high degree of accuracy.

When the target body is positioned deep in body tissue, the method can be improved: the needle device is guided through the vascular network to the target vessel before the needle protrudes and pierces the target vessel to the target site. Since the blood vessel is near almost every region of the body, the vessel wall is the primary target for intelligent dosing. Direct injection of therapeutic agents into the vessel wall in a circumferential manner is effective in treating diseases such as vascular disease, arterial restenosis, and in promoting angiogenesis in the ischemic heart. This delivery method may also be used with nerve ablative agents to achieve nerve ablation. Diseases that can be treated by ablating perivascular nerves are hypertension and diabetes, where denervated target blood vessels are the renal artery and hepatic artery, respectively.

Some vascular injection devices have been disclosed in the prior art and discussed below.

U.S. Pat. No.6,547,803 to Seward et al and U.S. Pat. No.7,666,163The micro infusion catheter includes a single needle connected to an inflatable elastic balloon. When the inflatable elastic balloon is inflated within the vessel, the needle is forced against the vessel wall, thereby penetrating the vessel wall. The needle may then be used to inject a therapeutic agent or a nerve ablative agent. Seward et al also describe another embodiment using two needles, but such a system would be difficult to miniaturize and would not be able to reach smaller vessels. Although->Micro-infusion catheters are capable of delivering therapeutic or nerve ablative agents to a target vessel, but have some drawbacks when used for vascular disease treatment and ablation treatment. First, if only a single needle is used, multiple passes are required to achieve circumferential delivery in the target vessel. Even so, it is difficult to control the precise rotation of the distal end of any device by operating at the proximal end, likely resulting in irregularly spaced injections. Second, the->Micro infusion catheters rely on balloon inflation and cannot achieve precise, controlled and adjustable penetration depths. Third, the maximum penetration depth achievable is limited. The maximum penetration depth depends on the length of the needle, but the maximum length of the needle is limited, as too long can affect the profile of the device. Thus, the drug cannot be injected to a sufficient depth that the device can provide limited therapy.

U.S. patent No.6,692,466 to Chow et al and U.S. patent No.7,273,469 to Chan et al disclose a catheter with a retractable needle inside the guide tube for injecting a drug into tissue. The distal portion of the guide tube is attached to a portion of the expandable member and the proximal portion of the guide tube is adhered to a tubular member attached to the expandable member. Although this device enables circumferential delivery at a precise, controllable and adjustable depth, there are also some drawbacks. First, since the guide tube must follow the contour of the balloon, securing the guide tube to the balloon and the tubular member limits the area in which the guide tube can bend. Abrupt changes in the direction of the guide tube may result in a smaller bend radius, thereby increasing the force required to move the needle out of the curvature, which increases the likelihood that the needle will be damaged or puncture the guide tube. Second, the guide tube is limited in material. Due to the small bending radius of the guide tube, the material used for the guide tube must be flexible. Chan et al mention the use of a sheath ring to prevent the guide tube from coming off, however, even with this construction the guide tube still needs to be flexible. This requirement for the guide tube limits the material to be polymeric, and metals and alloys may not be used. Third, it is difficult to achieve a large penetration depth to needle advancement ratio with the device. The optimum penetration depth to needle advance ratio is 1:1, which can only be achieved if the needle is perpendicular to the catheter axis. In this device, this ratio is determined by the balloon cone angle, typically between 20 and 40 degrees. One way to increase this ratio without changing the balloon taper angle is to use a distally curved needle. However, curved needles cannot be used because Chow and Chan cannot use hard materials for the catheter. Chow and Chan also mention the use of a ribbon/deflector made of hard material to prevent the guide tube from being pierced at the bend, but the curved needle would have the needle tip opposite the guide tube throughout the length of the movement, so the use of a ribbon/deflector on a curved needle is impractical.

Peregrine System described in Fischer et al, U.S. Pat. No.8,740,849 ^TM (Peregrine System ^TM ) With three equally spaced needle guide elements, the needle guide elements are moved outwardly into the centre of the catheter before the needle is deployed from within each needle guide element. The nerve ablative agent can be passed through these needles to achieve circumferential ablation of the target vessel. Although Peregrine system ^TM (Peregrine System ^TM ) Circumferential delivery can be achieved at precise, controlled and adjustable depths, but there are still some drawbacks in using a guide pin element to position the catheter within the target vessel. First, the Peregrine system in the target vessel ^TM (Peregrine System ^TM ) The guide pin elements are simultaneously extended at the same speed until all the guide pin elements are in contact with the inner wall of the target vessel. The centering method is suitable for circular blood vessels such as arteries, but for blood vessels such as veins with irregular or flat cross-sectional shapes, the centering method cannot enable medicines to be deposited in the circumferential direction in the blood vessels. If a guide pin member is used to force the target vessel to a circular shape, there is a risk of serious damage to the vessel due to the small contact area provided by the guide pin member. Second, the high pressure that may be generated between the contact point of the hollow guide pin element and the vessel wall risks damaging the vessel wall. Third, after the guide pin member is extended, there is a risk that the catheter will need to be repositioned. Unless the pressure between the needle element and the vessel wall is high, a small number of points of contact between the needle element and the vessel wall may not provide sufficient stability to the catheter. If the proximal end of the catheter is accidentally moved, it may cause displacement of the distal end of the catheter. If this occurs before the needle is extended, a simple repositioning is required. However, if this occurs after the needle is extended, serious damage to the blood vessel may occur. Fourth, it is difficult to achieve all needles with the same penetration depth. All contact points provided by the pin member are in one plane. Due to the Peregrine system ^TM (Peregrine System ^TM ) Both the needle element and the needle have a predetermined curved shape, and the plane of contact must be perpendicular to the target vessel in order for all the needles to reach the same penetration depth in the target vessel. If delivery of the medicament to a precise depth is required, then the Peregrine system is used ^TM (Peregrine System ^TM ) The accuracy required to achieve all injection points would be a challenge.

Accordingly, there is a need for an infusion catheter that overcomes the problems of the prior art described above.

Disclosure of Invention

The present invention provides a catheter for delivering a substance into tissue outside a physiological cavity. The catheter may be used to deliver therapeutic agents to prevent and/or treat a variety of diseases such as vascular disease, arterial restenosis, ischemic heart disease, and diseases requiring nerve ablation such as hypertension, diabetes, or chronic obstructive pulmonary disease.

Accordingly, the present invention provides the following.

1. A drug delivery device comprising:

an axially extending elongate member having a proximal portion, a distal portion, a first lumen and a second lumen;

an inflatable balloon coupled to said distal end portion of said axially extending elongate member, said inflatable balloon having proximal and distal ends coupled by a working portion, said inflatable balloon further having an outer surface and an inner surface, said outer surface and said inner surface defining a balloon lumen, wherein a first lumen of said axially extending elongate member is in fluid communication with said balloon lumen;

Two or more guide thimbles, each guide thimbles having a proximal end portion and a distal end portion, wherein the proximal end portion of each guide thimbles is connected with the axially extending elongate member; and

two or more needles, each having a lumen and being received in one of the guide thimbles, each of the needles being reversibly retractable from the distal portion of the guide thimbles receiving itself, wherein the second lumen of the axially extending elongate member is in fluid connection with the lumen of each of the needles;

wherein the distal end portion of each of the guide sleeves does not exceed an outermost diameter of the outer surface of the inflatable balloon when the inflatable balloon is inflated.

2. The drug delivery device of claim 1, wherein the inflatable balloon is coupled to the distal end of the axially extending elongate member.

3. The drug delivery device of claim 2, further comprising a balloon support element within the inflatable balloon, optionally coupled to the distal end portion of the axially extending elongate member and the distal end of the inflatable balloon, respectively.

4. The drug delivery device of claim 1 or 2, wherein the axially extending elongate member comprises a third lumen, optionally adapted for mounting the drug delivery device on a guidewire.

5. The drug delivery device of claim 1 or 4, wherein the inflatable balloon is disposed on the distal portion of the axially extending elongate member.

6. The drug delivery device of any of the preceding claims, wherein the distal portion of each of the guide sleeves is freely movable relative to the inflatable balloon and/or the distal portion of each of the guide sleeves is not fixed to the inflatable balloon.

7. The drug delivery device of any of the preceding claims, wherein the guide sleeves are arranged at uniform intervals around the outer circumference of the axially extending elongate member.

8. The drug delivery device of any of the preceding claims, wherein the distal end portion of the guide cannula is configured to contact an outer surface of the inflatable balloon and move with the outer surface of the inflatable balloon when the inflatable balloon is inflated.

9. The drug delivery device of claim 8, wherein the guide cannula is configured to at least partially return to its original shape when the inflatable balloon is deflated.

10. The drug delivery device of any of the preceding claims, wherein the inflatable balloon has a proximal taper, a middle cylindrical portion and a distal taper.

11. The drug delivery device of claim 10, referring to claim 8 or 9, wherein the distal portion of the guide cannula is configured to contact an outer surface of the proximal taper of the inflatable balloon.

12. The drug delivery device of any of the preceding claims, wherein each of the guide sleeves comprises a slit cut into one side of the guide sleeve.

13. The drug delivery device of any of the preceding claims, wherein the guide sleeve is made of a metal or an alloy.

14. The drug delivery device of any of the preceding claims, further comprising a sheath movably disposed on the axially extending elongate member.

15. The drug delivery device of claim 14, wherein the sheath has an extended state in which the sheath covers the entirety of the two or more guide cannulas and at least a portion of the inflatable balloon, and a retracted state in which the sheath does not cover a portion of the inflatable balloon, optionally in which the sheath covers only a portion of the two or more guide cannulas.

16. The drug delivery device of any of the preceding claims, wherein the needle is simultaneously reversibly retractable.

17. The drug delivery device of any of claims 1-15, wherein the needle is independently reversibly retractable.

18. The drug delivery device of claim 1, wherein each of the needles comprises a curved end portion, optionally each of the needles being configured to curve radially outwardly from the axially extending elongate member when the needle is extended from the guide cannula housing itself.

19. The drug delivery device of any of the preceding claims, wherein the second lumen of the axially extending elongate member comprises two or more sub-lumens, each of the sub-lumens being in fluid connection with the lumen of the needle, optionally the two or more sub-lumens being not in fluid communication with each other.

20. The drug delivery device of any of the preceding claims, further comprising a support structure for positioning the guide cannula and securing the guide cannula to the axially extending elongate member.

21. The delivery device of any of the preceding claims, wherein the distal end of the axially extending elongate member is connected to a flexible tip.

22. The drug delivery device of any of the preceding claims, wherein the drug delivery device is a rapid exchange catheter or a total exchange catheter.

23. The drug delivery device of any of the preceding claims, wherein at least one radiopaque element is included, optionally the radiopaque element is located within the balloon lumen, or on the axially extending elongate member, or on the guide cannula, and/or on the needle.

24. The drug delivery device of any of the preceding claims, further comprising a handle disposed at a proximal end of the axially extending elongate member.

25. The drug delivery device of claim 24, wherein the handle comprises structure for controlling a maximum depth of extension of the needle.

26. The delivery device of claim 24 or 25, wherein the handle comprises means for reversibly retracting the needle from the guide cannula.

27. The drug delivery device of claim 26, wherein the device comprises a first means for coarsely and reversibly retracting the needle and a second means for finely and reversibly retracting the needle.

28. The drug delivery device of any of claims 24 to 27, wherein the handle comprises a visual indicator indicating the depth of extension of the needle.

29. The drug delivery device of any of the preceding claims, wherein the guide cannulas comprise a bend at the distal end, optionally the distal end of each guide cannula being provided with an opening outwards from the catheter.

30. The drug delivery device according to any of the preceding claims, wherein,

each of the needles includes a curved end;

the distal portion of the guide cannula is configured to contact and move with the outer surface of the inflatable balloon; and is also provided with

After the inflatable balloon is deflated, the guide sleeve at least partially returns to its original shape,

Optionally, each of the needles is configured such that the curved end portion curves radially outwardly from the axially extending elongate member when the needle is extended from the guide cannula housing itself.

The present invention has several advantages over the previously described devices. By using a retractable needleThe device enables a larger penetration depth range to be achieved in a controlled manner. Peregrine System described in Fischer et al, U.S. Pat. No.8,740,849 ^TM (Peregrine System ^TM ) In contrast, using a balloon rather than a catheter to center and stabilize the device, the stability of the device is better because the inflatable balloon anchors the position of the device better than the catheter. Since the surface area of the balloon in contact with the lumen is much larger than when using a catheter, the use of a balloon reduces the pressure exerted on the lumen wall and thus reduces the risk of damaging the lumen wall. The use of a balloon makes the device also suitable for non-circular vessels, while the Peregrine system ^TM (Peregrine System ^TM ) The use of a guide pin element to locate at the center of a vessel is not suitable for use with non-circular vessels. Many veins are non-circular in nature, and the use of catheters to center and stabilize devices in such vessels is not optimal because the catheters can exert excessive pressure on certain points of the vessel wall. The balloon of the present invention forces the vessel to be rounded for optimal therapeutic effect, and thus the present invention is applicable to such non-circular vessels.

Drawings

Fig. 1 is a schematic view of a first embodiment of the invention, wherein the sheath is in an extended position.

Fig. 2 is a schematic view of a first embodiment of the invention with the sheath in a retracted position, the balloon in a deflated state, and the needle in a retracted position.

Fig. 3 is a schematic view of a first embodiment of the invention with the sheath in a retracted position, the balloon in an inflated state, and the needle in a retracted position.

Fig. 4 is a schematic view of a first embodiment of the invention with the sheath in a retracted position, the balloon in an inflated state, and the needle in an extended position.

Fig. 5 is an enlarged view of the distal region of the device of fig. 2.

Fig. 6 is an enlarged view of the distal region of the device of fig. 3.

Fig. 7 is a cross-section of three conduits of the device of fig. 3.

Fig. 8 is an enlarged view of the distal region of the device of fig. 4.

Fig. 9 is a cross-section of three catheters and three needles of the device of fig. 4.

Fig. 10 is a schematic view of an example of a handle.

Fig. 11 is a schematic view of one example of a possible support structure.

Fig. 12 is a schematic view of one example of another possible support structure.

Fig. 13 is a cross-section of an inflatable balloon and a flexible tip.

Fig. 14 shows the distal region of a second embodiment of the invention with the balloon in a deflated state and the two guide cannulas and needle in a retracted position.

Fig. 15 shows another embodiment of the distal region of the second embodiment of the invention, wherein the balloon is in an inflated state and the two guide thimbles and the needle are in an extended position.

Fig. 16 shows a cross section of the guide sleeve with a bend at the distal tip.

Figures 17 to 21 are possible cross-sections of catheter bodies in which the embodiments shown in figures 17, 18, 20 do not use a guide wire, whereas the embodiments shown in figures 19, 21 use a guide wire.

Detailed Description

The present invention provides a drug delivery device, i.e., a catheter (e.g., a rapid exchange catheter or a total exchange catheter), that is insertable into a blood vessel or lumen of a body to deliver a drug to tissue surrounding the blood vessel or lumen. The drug delivery device comprises:

In some embodiments, the drug delivery device comprises an inflatable balloon coupled to the distal end of the axially extending elongate member. The delivery device further includes a balloon support element (e.g., a wire or other element that prevents axial compression of the balloon) positioned within the inflatable balloon, the balloon support element being coupled to the distal end portion of the axially extending elongate member and the distal end of the inflatable balloon, respectively.

In some embodiments, an inflatable balloon is disposed at a distal portion of the axially extending elongate member. For example, the inflatable balloon is coupled to the distal end of the axially extending elongate member and is disposed on the distal end portion of the axially extending elongate member.

In some embodiments, the axially extending elongate member comprises a third lumen adapted to mount the drug delivery device on a guidewire. Thereby facilitating guiding the device to a target site of the vascular network.

The two or more guide thimbles are arranged at uniform intervals around the outer circumference of the axially extending elongate member.

In some embodiments, the distal portion of the guide sleeve may not be fixed to the inflatable balloon and/or may be free to move relative to the inflatable balloon. As explained herein, this enables the distal end of the guide cannula to assume a configuration/posture within the catheter that enables the needle to penetrate the catheter at a favorable angle (e.g., an angle that is substantially perpendicular to the catheter wall).

In some embodiments, the distal portion of the guide cannula is configured to contact an outer surface of the inflatable balloon and move with the outer surface of the inflatable balloon as the inflatable balloon is inflated. This also helps to enable the distal end of the guide cannula to assume a configuration/posture within the catheter that enables the needle to penetrate the catheter at a favorable angle (e.g., an angle that is generally perpendicular to the catheter wall).

However, when the guide sleeve is configured to contact the outer surface of the inflatable balloon and move with the outer surface of the inflatable balloon as the inflatable balloon is inflated, the guide sleeve may also be configured to at least partially return to the original shape or configuration after the inflatable balloon is deflated. Thus, it is ensured that the device can be easily withdrawn from the vessel after use without the need for a cannula which breaks the vessel wall, and likewise that the device can be reinserted into the vessel without the need for a cannula which breaks the vessel wall.

The inflatable balloon may include a proximal taper, a middle cylindrical portion, and a distal taper. In this embodiment, the distal portion of the guide cannula may be configured to contact and move with the outer surface of the proximal taper of the inflatable balloon. Thus, the guide cannula may be moved by inflation of the balloon such that when the balloon is fully inflated, the guide cannula assumes a position that facilitates penetration of the vessel wall by the in-tube needle.

The device may further comprise a support element at the proximal portion of each guide sleeve to secure it in place while allowing the distal portion of the guide sleeve to move and adopt a desired orientation during use. The distal tip of the guide sleeve may curve outwardly and terminate at a proximal taper of the balloon. This means that the distal tip of the guide sleeve does not extend beyond (i.e. in the radial direction) the outermost diameter of the balloon outer surface, and therefore the distal tip of the guide sleeve does not come into contact with the vessel wall when the guide is to the target site. Such contact between the guide sleeve and the vessel wall during the guide procedure may result in damage to the vessel wall.

The guide sleeve may have a slit cut into one side of the guide sleeve to control the direction of movement or deformation of the guide sleeve as the balloon is inflated.

In some embodiments, the needle includes a curved end. This has the advantage that the curved end portion is curved radially outwardly from the axially extending elongate member when the needle is extended from the cannula in which it is located. Based on this arrangement, the needle may be allowed to puncture the catheter at a more nearly perpendicular angle than a straight needle, thereby achieving a greater penetration depth to needle advancement ratio.

In embodiments where the needles have curved ends, each needle may be configured to curve radially outwardly from the axially extending elongate member as the needle extends from the cannula housing itself.

In some embodiments, the guide cannula may be distally provided with a bend that facilitates bending of the otherwise straight needle when the straight needle is extended from the guide cannula, or that facilitates extension of the curved needle when it is extended from the guide cannula.

In some embodiments, the distal end of each guide cannula is provided with an opening outward from the catheter, again to aid in bending and/or direction of the needle as it extends from the guide cannula.

In some embodiments, the guide sleeve is made of a metal or alloy. This arrangement is particularly advantageous in the case of needles having curved ends, since the needle tip may contact the edge of the guide cannula and the plastic cannula may be pierced or damaged by the curved needle tip. The use of a guide cannula made of metal or alloy is also advantageous in cases where it is desired that the needle be slightly deformed during extension or retraction. For example, a straight needle may be used in conjunction with a curved cannula to allow the needle to penetrate at a more nearly perpendicular angle than if a straight cannula were used.

Straight needles are advantageous because they are easier or less costly to obtain.

Alternatively, if the device is intended to have a smaller profile in the retracted needle state (which may be achieved with a straight cannula), the curved needle may be used in combination with the straight cannula, as well as the advantage of the angle of penetration of the curved needle.

In some embodiments, the device includes a sheath movably disposed on the axially extending elongate member. The sheath may be used to house the guide cannula and other components of the device as the guide device is advanced into and out of the target site to be treated to avoid damaging the device or vessel wall during the guide procedure.

In some embodiments, the sheath has an extended state in which the sheath covers all of the two or more guide thimbles and at least a portion of the inflatable balloon, and a retracted state in which the sheath does not cover a portion of the inflatable balloon. In some embodiments, the sheath covers only a portion of the two or more guide thimbles in the retracted state, whereby the needle is more flexible during use, while having the advantages discussed above.

The needles of the device of the present invention may be reversibly retractable simultaneously and/or may be independently reversibly retractable.

In some embodiments of the invention, the second lumen of the axially extending elongate member comprises two or more sub-lumens, each of the sub-lumens being in fluid connection with the lumen of the needle. In some embodiments, the two or more sub-lumens are not in fluid communication with each other. Thereby allowing different fluids (e.g., different active agents) to be administered through different needles.

In some embodiments, the device further comprises a support structure for positioning the guide sleeve and securing the guide sleeve to the axially extending elongate member. The extent of possible movement of the distal end of the guide cannula can thereby be controlled and the site of penetration of the needle through the vessel wall can be more accurately controlled.

In some embodiments, the distal end (e.g., distal tip) of the axially extending elongate member is connected to or has a flexible tip. Thereby avoiding damage to the vessel wall when the guiding device is delivered to the site to be treated.

In some embodiments, the device includes at least one radiopaque element to facilitate operator awareness of the device's position within the patient. In some embodiments, the radiopaque element may be located within the balloon lumen, or on an axially extending elongate member, or on a guide cannula, and/or on a needle.

A handle may be provided at the proximal end of the device, the handle comprising one or more of:

● A structure for controlling the maximum extension depth of the needle;

● A visual indicator indicating the depth of extension of the needle (e.g., a visual indicator indicating the depth of extension of the current needle for the operator to know the current state of the needle);

● Means for reversibly retracting the needle from the cannula (e.g., a first means for coarsely reversibly retracting the needle and a second means for finely reversibly retracting the needle);

● Means for extending and retracting the sheath;

● An inflation port of the balloon (i.e., an inflation port fluidly connected to the first lumen of the axially extending elongate member); and

● The inflation port of the needle (i.e., the inflation port fluidly connected to the second lumen of the axially extending elongate member).

As will be appreciated by those skilled in the art, these features assist the user in operating the device of the present invention in a safe and efficient manner.

In certain embodiments of the invention, the device may be a rapid exchange catheter or a total exchange catheter.

In one embodiment of the invention:

each of the needles includes a curved end;

the distal portion of the guide sleeve may be configured to contact the outer surface of the inflatable balloon and move with the balloon outer surface as the balloon is inflated; and is also provided with

After balloon deflation, the guide sleeve at least partially returns to its original shape.

In another example of this embodiment, each needle may be configured such that the curved end portions curve radially outward from the axially extending elongate member as the needle extends from the guide cannula housing itself.

Further details of the apparatus of the present invention and the use of the apparatus are described below.

In use, the device is first tracked into place, the balloon is in a deflated state and the sheath (if present) is positioned over at least a portion of the balloon and guide cannula, with the needle fully within the guide cannula. Once the device is in place, the sheath may be retracted, inflating the balloon, advancing the needle outwardly to the desired depth. Inflation of the balloon causes the distal end of the guide sleeve to push outward. With the inflatable balloon, the device is positioned in the center of the vessel while anchored in place. In addition, the guide cannula is placed over the proximal taper of the balloon, so that the inflatable balloon acts as a stabilizing platform for the guide cannula, providing optimal conditions for the needle to be advanced outwardly from the guide cannula to the vessel wall. Once the needle is in place, treatment can be performed by introducing a therapeutic agent through the needle. After treatment, the needle is retracted, the balloon deflated and the device is withdrawn.

The components of the device of the present invention are described in detail below.

The device is secured within the lumen when the balloon is inflated such that the surface of the balloon contacts the inner wall of the lumen. Typically, the inflatable balloon is coupled to the distal end of the axially extending elongate member and is disposed on the distal portion of the axially extending elongate member. Typically, the balloon is a low pressure balloon, i.e., is inflated to a relatively low pressure to avoid damage to the lumen/vessel. For example, the balloon may typically be inflated to a pressure of 3 atmospheres or less, for example about 2 atmospheres. During use, the balloon may be inflated from a contracted state (uninflated) to an expanded state (inflated). The balloon may be deflated after inflation to return to the contracted/deflated state so that the catheter may be moved to another target site or withdrawn from the body. The inflatable balloon may have a proximal taper, a middle cylindrical portion, and a distal taper.

In some embodiments of the invention, the axially extending elongate member may comprise a third lumen adapted for mounting the device on a guidewire. In catheter embodiments without a guidewire lumen, the balloon itself may risk bending or collapsing if the balloon is not supported as the catheter is moved distally within the lumen. Thus, when the device (catheter) does not include a guidewire lumen, a support element (e.g., a support wire) may be disposed within the balloon. A support element (e.g., a support wire) may be coupled to the catheter at two locations, a distal end of the balloon and a proximal end of the balloon, respectively. For example, the support element is connected to the distal end portion of the axially extending elongate member and the distal end of the inflatable balloon, respectively.

The device comprises two or more guide sleeves, such as 2, 3, 4, 5 or 6 guide sleeves, each of which houses a retractable needle. Typically, the device comprises 2 to 4 guide thimbles, such as 2 or 3 guide thimbles. The guide sleeves are typically arranged at even intervals around the circumference of the axially extending elongate member to ensure even administration of the drug to the tissue surrounding the lumen/vessel. The guide cannula is typically made of a strong hard material, such as one or more metals or alloys, thereby rendering the cannula rigid and capable of bending or deforming a needle disposed within and/or extending from the cannula. For example, the cannula may be straight and capable of deforming a curved needle tip such that the needle is received in the cannula.

Alternatively, the cannula may comprise a curved portion capable of deforming the straight needle, the straight needle extending out of the cannula through the curved portion of the cannula such that the curved portion of the cannula bends the needle. The proximal end of the guide sleeve may be connected to the catheter body with the distal end being a free end and terminating at or adjacent the balloon proximal taper. Typically, the guide catheters are arranged at uniform intervals around the catheter. The openings at the distal end of the guide sleeve are generally configured such that the open ends are all perpendicular to the axial direction of the catheter. In some embodiments, the distal end of the guide cannula terminates in a bend that facilitates bending of the needle tip as the needle extends from the guide cannula. In other embodiments, the guide sleeve may be straight.

In some embodiments of the invention, the distal portion of each guide sleeve is free to move relative to the inflatable balloon and/or is not fixed to the inflatable balloon. The distal portion of the guide sleeve may be configured to contact the outer surface of the inflatable balloon and move with the outer surface of the inflatable balloon when the balloon is inflated. This means that the balloon can be inflated to place the cannula in the desired position for the needle to extend. In this case, the guide sleeve is typically configured to at least partially return to its original shape when the inflatable balloon is deflated. In another configuration, the guide sleeve may terminate at the proximal end of the inflatable balloon so that the position of the guide sleeve is not affected by balloon inflation and deflation.

Typically, the distal end of the guide cannula may be provided to terminate before or at a region proximal to the proximal end of the balloon. This means that the guide sleeve is only moved near the proximal region of the balloon, which is generally tapered at its proximal end (i.e., proximal taper). Thus, when the balloon is fully inflated, the distal end of the guide sleeve does not extend beyond the outermost diameter of the balloon in the vertical direction. This is important to avoid the guide sleeve from striking the vessel/lumen wall during use, as such impact may cause damage to the vessel or lumen.

The guide sleeve may be supported by a support structure. The support structure is used to position the guide sleeve and secure the guide sleeve to the axially extending elongate member. Thus, the support structure may secure the proximal and intermediate portions of the sleeve, but the distal portion thereof may still flex outwardly as the balloon expands. Alternatively, the support structure may support and secure the entirety of the guide sleeve. In this case, the guide sleeve may be mounted in the support structure. The guide sleeve at least partially returns to its original shape after the balloon is deflated.

Each guide cannula houses a needle therein that is movably disposed within the lumen of the guide cannula such that each needle has an extended state and a retracted state. The distal end of each needle may be bent laterally outward from the catheter (i.e., each needle may include a bent end). Thus, a typical arrangement of the needle is as follows: the curved end of each needle is bent radially outwardly from the axially extending elongate member as the needle extends from the cannula housing itself. Generally, the radius of curvature of the needle is larger than the guide cannula in which it is located. In this case, the bend at the distal end of the guide cannula forces the needle to adopt a curvature of smaller radius as the needle transitions from the retracted state to the extended state. Since the needles are connected to the delivery sheath, the needles are in fluid communication with each other and the proximal end of the catheter. The needles may be reversibly retractable simultaneously, and/or independently reversibly retractable.

Each needle includes a lumen that is in fluid communication with a lumen (e.g., a second lumen) in the axially extending elongate member so that fluid can be delivered into the needle along the axially extending elongate member. The second lumen of the axially extending elongate member may comprise two or more sub-lumens, each sub-lumen being in fluid connection with the lumen of the needle. Typically, there is no fluid communication between two or more sub-lumens.

The distal end of the device may be provided with a flexible tip which is connected to the distal end of the axially extending elongate member. The proximal end of the device is typically provided with a handle by which the needle can be manipulated from the extended state to the retracted state and vice versa. The handle may include indicia for determining needle displacement to assist in controlling the penetration depth of the needle into the lumen wall and surrounding tissue. The handle may also include structure to set the maximum penetration depth of the push needle hour hand. The structure is typically lockable and releasable whereby the structure can be easily and quickly released when further needle advancement is required. The handle may include means to convert rotational motion into lateral displacement, such as by using threads to reduce the force required for needle displacement.

The device may include at least one radiopaque element, i.e., an element that is visible under fluoroscopy or other imaging methods. At least one radiopaque element may be provided at a location that aids in catheter positioning, for example, within a balloon lumen, on an axially extending elongate member, on a guide cannula, and/or on a needle. Radiopaque elements may also be provided on the flexible tips, if any. Thus, when the catheter is directed to a target site in the body, suitable imaging techniques may be used to provide accurate real-time information about the catheter's position in the body.

The device may include a sheath movably disposed over the axially extending elongate member. The sheath is typically movably arranged on the portion of the axially extending elongate member having the guide sleeve, i.e. the sheath is movably arranged on the guide sleeve. The sheath generally has an expanded state and a retracted state, and in some embodiments is operable by a handle. In the extended state, the distal end of the sheath may be distal to the distal end of the guide cannula such that the sheath covers the entirety of the guide cannula and at least a portion of the inflatable balloon. In the retracted state, the distal end of the sheath is generally adjacent the proximal taper of the balloon and thus does not cover a portion of the balloon. In the retracted state, the sheath typically covers only a portion of the cannula. Thus, in the extended state, the sheath covers the cannula and protects the vessel/lumen wall from the cannula while moving along the vessel. In the retracted state, the cannula is exposed inside the blood vessel so that the needle can extend out and penetrate the vessel wall. In a variable embodiment, the sheath may be a flexible sheath and overlie the proximal taper of the balloon, the sheath being forced upon balloon expansion as the balloon expands, the sheath being naturally withdrawn. In another alternative embodiment, the sheath may be rigid and cover the distal end of the guide cannula, with the sheath providing a weak point above the guide cannula. During tracking of the catheter to the target site, the rigid sheath will cover the distal end of the guide cannula, but when the balloon is inflated, the diameter of the balloon expands causing the rigid sheath to tear at the weak point, exposing the distal end of the guide cannula so that the needle can be extended smoothly.

The device may include a handle disposed at the proximal end of the axially extending elongate member, the handle having several different uses. The handle is provided with infusion and inflation luer ports to allow for the infusion of substances therethrough via the needle and inflation of the balloon. With the sheath, the handle may also be provided with a flush luer port to flush the interior of the sheath. The needle may be manipulated from the retracted state to the extended state and vice versa by the handle. Preferably, the manipulation of the needle to the desired depth is carefully controlled to help avoid damaging the tissue while ensuring that the drug is injected into the correct tissue. The handle may include structure for controlling the maximum extension depth of the needle. The handle may further comprise means for reversibly retracting the needle from the guide cannula, for example comprising first means for coarsely reversibly retracting the needle and second means for finely reversibly retracting the needle. For example, gears or screws may be provided on the handle to fine control the extension and retraction of the needle and the maximum depth of extension. In addition, the device may also reduce the force required to move the needle. The handle may include indicia to assist the user in determining the displacement of the needle relative to the catheter as it extends from the guide cannula. The handle is also used to determine or set the fully deployed state and the fully retracted state. When the needle cannot be retracted further, the fully retracted state of the needle is obtained. In embodiments where the curved needle is used in combination with a guide cannula having a free end and without a sheath, the fully retracted state is important because the needle must be retracted far enough to ensure that the guide cannula does not bend outwardly. In order to avoid damage to sensitive tissues caused by excessive needle extension, it is important to preset the maximum extension state.

In an embodiment of the invention:

each needle includes a curved end;

the distal portion of the guide sleeve is configured to contact and move with the outer surface of the inflatable balloon; and is also provided with

After balloon deflation, the guide sleeve can at least partially return to its original shape,

optionally, wherein each needle is configured such that when the needle protrudes from the cannula housing itself, the curved end portion is curved outwardly from the axially extending elongate member.

The present invention will be described in detail with reference to the accompanying drawings.

Fig. 1 to 4 show a device according to a first embodiment of the present invention. Fig. 1-4 are side views of the device 100 at various stages of use. In fig. 1, the device 100 is in a sheath covered state with the sheath 101 fully extended. The sheath 101 may protect the lumen wall as the device is tracked through the sheath 101. At the distal portion of the device is a flexible tip 102, thereby providing good trackability of the device 100 through the lumen. The handle 103 of the device comprises a slider 111 for controlling the displacement of the sheath 101. The device also includes an inflation luer port 112 (for inflating inflatable balloon 121), a flush luer port 113 (for flushing the interior of sheath 101), an injection luer port 114 (allowing fluid to enter needle 123), a nut 115 (controlling the displacement of needle 123), and a bolt 116 (for moving needle 123). Fig. 1 shows the state in which the device 100 is being tracked to a treatment location. After the device 100 is tracked to position, the sheath 101 will be retracted.

Fig. 2 shows the device after the slider 111 has been advanced proximally to the retracted position, the sheath 101 is in the retracted state. Retraction of the sheath 101 exposes the balloon 121 and the guide cannula 122. When the sheath 101 is in the retracted position, the balloon may be deployed (inflated).

Fig. 3 shows the device 100 in a state in which the balloon 121 is inflated. Inflatable balloon 121 secures the catheter to the vessel wall and centers the catheter in the lumen. The inflation of balloon 121 also causes the distal end of guide sleeve 122 to displace outwardly. Once the device is in place and secured, the nut 115 may be rotated relative to the handle 103 to push the needle 123 forward. Fig. 4 shows the device in a state where the needle 123 is extended.

Fig. 5 to 9 are views of the distal portion of the device according to the first embodiment of the present invention at a stage of non-use. Fig. 5 shows a distal portion of the device as shown in fig. 2. When balloon 121 is deflated, guide sleeve 122 is mostly straight, and the distal end of guide sleeve 122 may be located within the folds of balloon 121. Fig. 6 shows the distal portion of the device shown in fig. 3 after inflation of balloon 121. In the inflated state, the guide sleeve 122 is in contact with the balloon 121, and the balloon 121 pushes the distal end of the guide sleeve 122 to bend it outwards. Fig. 7 shows a lateral view of the distal end of the device 100 when the balloon 121 is viewed from the proximal end in fig. 3. It is particularly important that the guide sleeve 122 does not extend beyond the outermost diameter of the balloon 121. This is because an excessively long guide cannula may contact the lumen wall, potentially causing injury during balloon inflation. In addition, the guide cannula may prevent the balloon from directly contacting the lumen wall, resulting in poor anchoring of the device.

Fig. 8 shows the distal portion of the device as shown in fig. 3 when the balloon 121 is inflated and the needle 123 is extended. Preferably, the exposed portion of the needle is bent outwardly in the same direction as the distal end of the guide cannula, thereby achieving a greater penetration depth and better control of the penetration depth. Fig. 9 shows a lateral view of the distal end of the device 100 when the balloon 121 is viewed from the proximal end in fig. 4.

Fig. 10 is a schematic view of an example of the handle 103. In this example, the proximal end of the handle is used to control movement of the needle. When the nut 115 is rotated, the mating surface therein engages the threads on the bolt 116, and the bolt 116 is coupled to the needle 123 such that the needle 123 moves. The penetration depth of needle 123 may be determined by indicia 131 on the handle.

Fig. 11 and 12 show examples of support structures. The support structure is used to ensure that the guide sleeve is in the correct position of the catheter. The support structure shown in fig. 11 has four lumens, a central lumen 201 being located in the center of the device to accommodate any portion of the catheter, such as an inflation tube extending proximally from the balloon. In the support structure shown in fig. 11, three outer lumens 202 are equally spaced around a central lumen 201 for receiving a guide cannula. The support structure shown in fig. 11 is adapted for placement at the proximal end of the balloon. The support structure shown in fig. 12 has evenly spaced grooves 203, in which grooves 203 guide bushings can be placed. The support structure shown in fig. 12 may be positioned on the proximal taper of the balloon to provide support at a more distal location. These support structures may be used independently, but when used together, these support structures may cooperate to ensure the orientation of the guide sleeve.

Fig. 13 is a cross-section of a possible configuration of balloon regions. In some embodiments of the present device, a guidewire is not used. A guidewire may be used in conventional balloon catheters to support the soft balloon. In embodiments of the invention that do not require the use of a guidewire, a support wire 206 may be used to support balloon 205. The support wire 206 is connected to a distal balloon strut 207 and a proximal balloon strut 208. The distal end of the balloon may be connected to a flexible tip 204 to enhance trackability of the device.

Fig. 14 and 15 show devices according to a second embodiment of the invention, showing the distal end regions of the device 300 at different stages of use, respectively. In the device 300 according to the second embodiment, a plurality of guide sleeves (not shown) are accommodated in a support structure 302 fixed to the elongate member. The guide sleeve does not include any "free" portion that moves with the balloon. Instead, each guide sleeve terminates before the balloon 301 and is therefore not in contact with the balloon 301.

Fig. 14 shows the device 300 with the balloon 301 in a deflated state and the needle 303 in a retracted position, which is the state in which the device 300 is being tracked into place. Fig. 15 shows the device 300 with the balloon 301 inflated and the needle 303 extended.

Since the guide cannula terminates before the balloon 301, it is critical that the needle 303 extending from the guide cannula have a radius of curvature small enough to ensure that the inflatable balloon 301 is not pierced.

Fig. 16 shows the distal end of the guide sleeve 209 terminating at a bend 210. In order to keep the profile of the device small, the curvature 210 should be arranged to be short so that the profile of the guide sleeve 209 does not increase significantly. The distal bend 210 advantageously allows the needle to protrude from the guide cannula at an angle. The bending portion 210 deforms the needle protruding from the guide sleeve 209 into a bent shape. Both of which are beneficial to various embodiments of the device.

Figures 17 and 18 show cross-sections of two possible configurations of catheter body in embodiments of devices that do not require a guidewire. Although the sheath is not shown in both figures, a sheath may also be present therein. Fig. 17 shows a body structure with two parts: a dual lumen tube 401 and a syringe 403. The dual lumen tube 401 contains an inflation lumen 402 (i.e., a first lumen) and a syringe 403 including a second lumen. The syringe 403 is movable relative to the dual lumen tube 401 to allow for needle advancement and retraction. The dual lumen tube 401 is also directly connected to the balloon so that the balloon can be inflated and deflated through the inflation lumen 402. Fig. 18 shows a body structure with three parts: a dual lumen tube 404, a syringe 406 and an inflation tube 405. The structure shown in fig. 18 is similar to that shown in fig. 17, but the dual lumen tube 404 is not directly connected to the balloon. In fig. 18, inflation tube 405 is directly connected to the balloon for inflation and deflation. The inflation tube 405 is also not movable relative to the dual lumen tube 404.

Fig. 19 shows a cross section of a possible configuration of the catheter body in an embodiment of the device requiring a guidewire. The three lumen 411 contains an inflation lumen 412 (i.e., a first lumen), a syringe 414 including a second lumen, and a guidewire 413. Similar to fig. 17 and 18, a sheath may be provided and a syringe 414 is movable relative to the triple lumen 411 to control the needle. The balloon may also be connected directly to the tri-lumen tube 411 for inflation and deflation through the inflation lumen 412 or to a separate inflation tube located within the inflation lumen 412, similar to that shown in fig. 18.

Fig. 20 and 21 show cross-sections of two possible configurations of catheter body in an embodiment of the device with sheath. Fig. 20 shows a cross section of a possible configuration of a catheter body in an embodiment of the device, which does not require a guidewire, consisting of a sheath 501, an inflation tube 502 containing a first lumen, a syringe 503 containing a second lumen, and a body tube 504. The syringe 503 is housed inside and movable relative to the body tube 504. The sheath 501 accommodates the inflation tube 502 and the body tube 504, and is movable relative to the inflation tube 502 and the body tube 504. The inflation tube 502 and the body tube 504 may be connected together by an adhesive or around them using a heat shrink tube.

Fig. 21 shows a cross section of a possible structure of a catheter body in an embodiment of the device, which requires a guidewire, consisting of a sheath 511, a guidewire tube 512, an inflation tube 513 comprising a first lumen, two body tubes 514, 516 and two needles 515, 517. The needles of the device embodiment shown in fig. 21 are independent of each other and the second lumen comprises two sub-lumens formed within the body tubes 514, 516. The needles 515, 517 are located within the body tubes 514, 516, respectively, and are movable relative to the body tubes 514, 516, each body tube 514 or 516 constituting a sub-lumen of the second lumen. The sheath 511 houses and is movable relative to a guidewire tube 512, an inflation tube 513, and two body tubes 514, 516. The guidewire tube 512, inflation tube 513, and body tubes 514, 516 may be connected together by an adhesive or with heat shrink tubing around them.

A first embodiment of the present invention is described with reference to fig. 1 to 9. The device according to the first embodiment comprises three guide sleeves, the distal ends of which terminate in the proximal taper of the balloon, adjacent the proximal end of the working length of the balloon, so that the guide sleeves can flex outwardly as the balloon inflates. Each guide cannula houses a retractable needle which is bent laterally at the distal end in a direction outwardly of the catheter. The guide thimbles are evenly distributed around the catheter and supported by the support structure. The support structure is supported at the proximal end and intermediate region of the cannula to prevent unwanted movement, but the distal end of the cannula may move as the balloon expands. The device includes a support wire that supports the balloon to prevent collapsing or collapsing of the balloon, and a flexible tip to improve trackability of the device. Although not shown, as will be appreciated by those skilled in the art, the device of the first embodiment may include a retractable sheath as described in detail herein to cover the cannula as the catheter is guided along the blood vessel to the target site. In some cases, this first embodiment may include a sheath covering the balloon and the guide sleeve.

With reference to fig. 14 and 15, a second embodiment of the present invention is described. In this embodiment, the device includes two guide sleeves that terminate before the balloon (i.e., at the proximal end of the balloon) so that the guide sleeves are not affected by the balloon when the balloon is inflated. This means that the distal end of the guide cannula will not be displaced by the balloon dilation, so the needle must have a certain curvature to ensure that the needle does not puncture the balloon when it is extended from the guide cannula. This can be achieved by using a needle with a natural curvature, which means that the needle assumes a curved form once it is no longer constrained by the cannula. Alternatively, the cannula may include a curved distal portion whereby the needle is curved as it extends from the cannula. The sleeve is supported by the support structure, but in this embodiment the distal end of the sleeve need not move with the expansion of the balloon, so the support structure can support the entire sleeve in place. In the embodiment shown, the device does not include a flexible tip, although one skilled in the art can readily arrange it in this embodiment. The device includes a cannula/lumen for guiding a guidewire through the device. In some cases, this second embodiment may include a sheath covering the balloon and the guide sleeve.

A third embodiment of the invention corresponds to the first embodiment except that this embodiment does not include a supporting guidewire or flexible tip, but rather includes a lumen or cannula through which the guidewire is guided. This third embodiment likewise comprises two or more guide sleeves.

The fourth embodiment of the invention corresponds to the first embodiment, except that the present embodiment comprises two guide sleeves, one needle in each sleeve, instead of three sleeves/three needles. The specific embodiments described above (e.g., first, second, third, and fourth embodiments) may be modified to include any of the other functions disclosed herein. For example, each particular embodiment may be modified to include a sheath that covers the balloon and the guide sleeve. All embodiments disclosed herein can be modified to include a catheter/lumen that provides a passageway for a guidewire; or a support wire, and particularly preferably incorporates a flexible tip. Typically, the device will not include both a support wire and a lumen for a guidewire, as the use of a guidewire may render the support wire superfluous. In general, when a support wire is used, it is preferable to use a flexible tip in combination (because the support wire does not guide the passage of the device, but merely the structure of the support balloon), but when a guidewire is used, the guidewire can guide the device through the vessel, where a flexible tip is unnecessary. Finally, any of the first through fourth embodiments may include a radiopaque element.

In general, devices for larger vessels may include a support wire and a flexible tip, while devices for smaller, more peripheral vessels may be used in conjunction with a guidewire to facilitate navigation within a narrower vessel. Furthermore, a smaller number of needles, such as two needles, may be used for devices for smaller blood and the profile of the guide cannula that fits the needles is smaller than for larger blood vessels. For example, for devices for smaller vessels, the guide cannula is not placed over the balloon, but is instead placed in front of the balloon to obtain a smaller profile.

As will be appreciated by those skilled in the art, although the embodiments described herein have particular features, the apparatus provided by the present invention may have any technically reasonable combination of features of the present description, for example any technically reasonable combination of features of the first to fourth embodiments described herein.

A brief description of the method of use of the catheter of the present invention is provided below. The method can be used for all embodiments of the device. The method may include the following steps.

1. The tracking catheter is brought into the desired position in the deflated and needle retracted state.

2. Optionally using fluoroscopy or other imaging techniques to confirm that the catheter is in place.

3. The balloon is optionally inflated to a suitable pressure, for example 2 atmospheres, by a handle.

4. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been inflated and that the guide cannula is in place.

5. The needle is selectively operated from the retracted position to the extended position by a handle.

6. The substance for treatment is optionally injected through the needle into the target body via the handle.

7. The needle is optionally operated from the extended position to the retracted position by a handle.

8. The balloon is optionally deflated by a handle.

9. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been deflated and that the guide sleeve is in the deflated position.

10. If multiple injections are required, repeating steps 1-9.

11. After all injections are completed, the catheter is withdrawn from the body.

As described herein, the catheter may include a sheath that covers the guide cannula to prevent the guide cannula from damaging the vessel wall. When the catheter includes a sheath, examples of methods of use are as follows.

3. The sheath is retracted to a retracted state.

4. The balloon is optionally inflated to a suitable pressure, for example 2 atmospheres, by a handle.

5. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been inflated and that the guide cannula is in place.

6. The needle is selectively operated from the retracted position to the extended position by a handle.

7. The substance for treatment is optionally injected through the needle into the target body via the handle.

8. The needle is optionally operated from the extended position to the retracted position by a handle.

9. The balloon is optionally deflated by a handle.

10. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been deflated and that the guide sleeve is in the deflated position.

11. The sheath is extended to an extended state.

12. If multiple injections are required, repeating steps 1-11.

13. After all injections are completed, the catheter is withdrawn from the body.

In embodiments without a sheath, there is a risk that the guide cannula may cause damage to the vessel wall. To prevent this, a guide catheter may be used. An example method for using a catheter in combination with a guide catheter is provided below. The method is applicable to all embodiments of the device, although generally for embodiments without a sheath.

1. The guide catheter is tracked until the distal end passes the treatment site.

2. The tracking catheter is brought into the desired position in the deflated and needle retracted state.

3. Optionally using fluoroscopy or other imaging techniques to confirm that the catheter is in place.

4. The guide catheter is pulled back until the distal end of the guide catheter is near the distal end of the support structure (if any).

5. The balloon is optionally inflated to a suitable pressure, for example 2 atmospheres, by a handle.

6. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been inflated and that the guide cannula is in place.

7. The needle is selectively operated from the retracted position to the extended position by a handle.

8. The substance for treatment is optionally injected through the needle into the target body via the handle.

9. The needle is optionally operated from the extended position to the retracted position by a handle.

10. The balloon is optionally deflated by a handle.

11. Optionally using fluoroscopy or other imaging techniques to confirm that the balloon has been deflated and that the guide sleeve is in the deflated position.

12. If multiple injections are required, repeating steps 1-11.

In all embodiments of the catheter, the position of the distal end of the guide catheter and the distal end of the support structure during use is important for catheter positioning. The distal end position of the guide cannula determines the position of the needle penetrating the vessel/lumen wall and is therefore important, so that the distal end of the guide cannula can be used for positioning of the catheter at the target site. It is also important that the distal position of the support structure supports the various components of the catheter in place. Thus, the proximal portion of the support structure generally does not undergo dimensional changes when the balloon is inflated. It can be seen that when using a sheath or guide catheter, it is particularly important to ensure that the distal end of the sheath or guide catheter is close to the distal end of the support structure prior to inflation of the balloon. To facilitate visualization of the distal end of the guide cannula during use, the entire guide cannula may be made of a radiopaque material, or a radiopaque material may be provided at the distal end of the guide cannula. Another way to make the distal end of the guide cannula visible is to provide radiopaque material within the balloon, such as over the guidewire lumen or support wire, or any similar structure at the distal end of the guide cannula. To facilitate visualization of the support structure distal end during use, the entire support structure may be made of a radiopaque material, or the radiopaque material may be disposed at the support structure distal end. To facilitate visualization of the distal end of the sheath during use, a radiopaque material may be provided at the distal end of the sheath. The method of visualizing the distal end of the guide cannula, support structure and sheath is not limited to the above-described method. The radiopaque materials described herein may be used alone or in combination.

In an embodiment of the invention, the distal end of the guide cannula terminates in a bend that is used to determine the curvature and direction of the protruding needle. In these embodiments, since the radius of curvature of the distal end of the guide cannula is always smaller than the radius of curvature of the housed needle (i.e., the tighter bend), the radius of curvature of the needle becomes smaller as the needle is forced through the guide cannula having the tighter curvature as it moves from the retracted position to the extended position. During this process, the direction of curvature of the needle will also follow the direction of curvature of the guide cannula. By guiding the cannula to set the radius and curvature direction of the needle, the penetration depth of the needle can be more precisely controlled. Another benefit of bending at the distal end of the guide cannula is that a straight needle may be used, and a bent guide cannula may force the straight needle to bend as it exits the cannula. The radius of curvature used by the needle depends on the curvature that is present at the distal end of the guide cannula. The use of a straight needle is advantageous because it avoids deformation of the needle during storage of the straight cannula, which may be caused by curved needles.

When the needle is bent outwards in the extended position, the force required to move the needle from the retracted position to the extended position is greater and vice versa. There are several reasons for the greater force required. If a curved needle is used, the needle will be constantly pressed against the inner wall of the guide cannula, whereby the resulting friction may require a large force to overcome. In addition, when the curved needle is retracted from the extended position to the retracted position, a force is required to bend the needle from the curved configuration to the straight configuration. If the distal end of the guide cannula is curved, the radius of curvature of the needle becomes smaller and thus requires a large force as the needle moves from the retracted position to the extended position. Since great force is required to move the needle in either direction, it is particularly important that the portion of the distal end of the device that is connected to the handle be made of a material that does not stretch, as this will affect the safety and performance of the device. Metals or alloys may provide the desired properties but are too rigid. One way to overcome the rigidity of metal or alloy tubes is to pattern the tube by laser cutting to increase its flexibility. Because of the large force required, means, such as gears or threads, may be provided on the handle to amplify the force applied to the needle.

In catheter embodiments where the distal end of the guide cannula is the free end, there is a risk of damage to the lumen inner wall by the distal end of the guide cannula during initial catheter tracking to the target site. One possible solution is to place the distal end of the guide cannula within the folds of the collapsible balloon when the catheter is first inserted into the lumen and tracked to the target site, thereby preventing the distal end of the guide cannula from directly interacting with the lumen inner wall, thereby protecting the lumen inner wall. The distal end of the guide sleeve may be placed within the balloon folds either during or after the fold. For optimal effect, the number of folds should be equal to the number of guide sleeves, thereby providing the longest balloon folds for this number of guide sleeves. Another possible solution is to attach a soft material at the distal end of the guide cannula, which soft material may cover the entire periphery or part of the distal end. The soft material may be a low durometer polymer without any impediment to needle movement. Another possible solution is to use a sheath as described above movably arranged on the guide sleeve. The sheath will cover the distal end of the guide cannula during catheter tracking to the target site. Once the catheter is in place, the sheath is retracted exposing the distal end of the guide cannula so that the needle can be smoothly extended. Another possible solution is to provide a flexible sheath at the distal end of the guide cannula. During tracking of the catheter to the target site, the flexible sheath will cover the distal end of the guide cannula, but when the balloon is inflated, the balloon expands in diameter and the angle between the guide cannula increases, causing the flexible sheath to peel off, exposing the distal end of the guide cannula, allowing the needle to extend smoothly. Yet another possible solution is to provide a rigid sheath at the distal end of the guide cannula and to form a weak point in the rigid sheath, with the weak point being located above the guide cannula. During tracking of the catheter to the target site, the rigid sheath covers the distal end of the guide cannula, but when the balloon is inflated, the diameter expansion of the balloon will cause the rigid sheath to tear at the weak point, exposing the distal end of the guide cannula so that the needle can be extended smoothly. As will be appreciated by those skilled in the art, the device may comprise a combination of features intended to prevent damage to the vessel/lumen wall and is not limited to the possible solutions described above. These suitable features may be used alone or in combination.

In catheter embodiments where the distal end of the guide catheter is the free end, there is one possibility that there will be no preferential shaft bending: the guide sleeve is not only bent outwards, but also bent transversely. One possible solution is to change the guide sleeve to bend preferentially in only one direction. This may be accomplished by various methods, such as cutting one or more slits into the guide sleeve with a laser, making the guide sleeve easier to bend, or using a shaped guide sleeve. Another method is to make the guide sleeve of materials of different stiffness so that the guide sleeve bends in a specific direction. As will be appreciated by those skilled in the art, any method may be used to minimize the likelihood of the guide sleeve bending in the lateral direction.

In catheter embodiments using distally curved needles, long storage of the curved needle body in a straight configuration may risk leading to an increase in the radius of curvature of the needle. Fischer et al, in U.S. Pat. No.8,740,849, studied this problem and suggested a solution to place the needle in an extended state during storage. The needle is stored in an extended state when there is no obstruction at the distal opening of the guide cannula. However, where a sheath or guide cannula is used to be placed within the folds of the collapsible balloon, both the sheath and folds will cause a blockage to the needle. One possible solution for the sheath is to put the sheath in a retracted state during storage, thereby not blocking the needle. One possible solution for the folds is to arrange the needle tip in an angled direction during storage so that the needle avoids the folds when it is extended outwards in use. This may be accomplished by rotating an infusion cannula attached to the needle. The rotation may be by the handle and the angle of rotation and outward position may also be marked on the handle to ensure proper positioning. How such a catheter is ready for use is illustrated below.

1. The distal end of the guide cannula is placed within the collapsed balloon folds.

2. The needle is oriented in an angled position.

3. The needle is slowly and carefully extended to ensure that the needle does not damage the balloon.

4. The catheter is packaged and stored until use.

5. Prior to use, the needle is retracted to a fully retracted state.

6. The needle is set to an outward position.

7. Catheters were used as described above.

In catheter embodiments with a sheath, there is a potential for air to be released from the sheath as the sheath moves from an extended state to a retracted state within the lumen. If the lumen is a vessel that flows into a small vessel, the released air can form bubbles and cause air embolism, thereby creating a hazard to the patient. One way to significantly reduce the risk of air embolism is to flush the lumen of the sheath with water, preferably before the catheter is inserted into the patient.

In some embodiments, the distal end of the guide sleeve is a free end and terminates at a balloon proximal taper. The distal end of the guide sleeve being a free end means that when the balloon is inflated, the inflated balloon will exert an outward force on the guide sleeve, bending the free distal end outwards. Since the distal end of the guide cannula is a free end, the guide cannula bends more gently. This arrangement allows for less force to move the needle from the retracted position to the extended position and vice versa than the devices described in U.S. patent No.6,692,46 to Chow et al and U.S. patent No.7,273,469 to Chan et al. Based on the arrangement that the distal end of the guide sleeve terminates at the proximal taper of the balloon, when the balloon is fully inflated, the distal end of the guide sleeve does not exceed the outermost diameter of the balloon in the vertical direction, thereby reducing the likelihood of vessel damage caused by contact between the hollow distal end of the guide sleeve and the vessel wall. The use of a low pressure balloon may also reduce the likelihood of vascular injury. At the same time, inflation and expansion of the balloon also positions the distal tip of the guide sleeve adjacent the inner wall of the vessel. The guide cannula is supported by the balloon, and the distal tip of the guide cannula is close to the inner wall of the blood vessel, based on which the guide cannula can provide radial and lateral stability to the needle as it passes through the target vessel wall, thus allowing the use of a thinner needle.

A balloon may be used to support and position the guide cannula prior to needle extension. Such a balloon is described in U.S. patent No.6,283,947 to Mirzaee, although the reasons for using the balloon are different. In the prior art described by Mirzaee, the purpose of this balloon is mainly to guide the injection port angularly away from the catheter shaft and into the arterial wall. In the present invention, the balloon has several uses. As previously described, the inflated expansion of the balloon is used to position and support the guide cannula. After expansion, the balloon fills the lumen, with the balloon wall in contact with the lumen wall. Thus, 1) the catheter is centered with respect to the lumen such that each needle has the same penetration depth when protruding outward; 2) The distal end of the catheter is fixed in the lumen, so that accidental displacement can be prevented; 3) The lumen may have an irregular or flattened cross-sectional shape to allow for circumferential deposition of the drug. Thus, the present invention is applicable to a variety of different physiological chambers, and is not limited to physiological chambers having a circular cross-section.

Greater penetration depth may be achieved using a needle with a pre-bent end. The use of needles with pre-curved ends has been described in the prior art. However, existing infusion catheters do not provide adequate support for the needle, thus impeding the use of thinner needles. Peregrine System described in Fischer et al, U.S. Pat. No.8,740,849 ^TM (Peregrine System ^TM ) A needle with a pre-bent end supported by another structure is used, so that a thinner needle can be used. The invention and Peregrine system ^TM (Peregrine System ^TM ) The two main differences are that in the present invention the guide cannula is positioned before the needle is extended and that the present invention uses a balloon during catheter positioning and needle extension. These features of the present invention overcome the Peregrine system discussed above ^TM (Peregrine System ^TM ) Is not limited to the above-mentioned method.

In the embodiments and aspects of the invention described above, certain features are described in the singular or plural. As used herein, references to the singular are to be construed to include the plural and vice versa where technically reasonable. For example, where technically reasonable, such as when the device includes a plurality of guide thimbles, the one guide thimbles in question may include a plurality of guide thimbles.

Claims

1. A drug delivery device comprising:

two or more needles, each having a lumen and being received in one of the guide thimbles, each of the needles being reversibly retractable from the distal portion of the guide thimbles receiving itself, wherein the second lumen of the axially extending elongate member is in fluid connection with the lumen of each of the needles; wherein, the liquid crystal display device comprises a liquid crystal display device,

the distal end portion of each of the guide sleeves does not exceed an outermost diameter of the outer surface of the inflatable balloon when the inflatable balloon is inflated.

2. The drug delivery device of claim 1, wherein: the inflatable balloon is connected to the distal end of the axially extending elongate member.

3. The drug delivery device of claim 2, wherein: further comprising a balloon support element located within the inflatable balloon, optionally connected to the distal end portion of the axially extending elongate member and the distal end of the inflatable balloon, respectively.

4. The drug delivery device of claim 1 or 2, wherein: the axially extending elongate member comprises a third lumen, optionally adapted to mount the drug delivery device on a guidewire.

5. The drug delivery device of claim 1 or 4, wherein: the inflatable balloon is disposed on the distal end portion of the axially extending elongate member.

6. The drug delivery device of any of the preceding claims, wherein: the distal portion of each of the guide sleeves is freely movable relative to the inflatable balloon and/or the distal portion of each of the guide sleeves is not fixed to the inflatable balloon.

7. The drug delivery device of any of the preceding claims, wherein: the guide thimbles are arranged at uniform intervals around the outer circumference of the axially extending elongate member.

8. The drug delivery device of any of the preceding claims, wherein: the distal portion of the guide cannula is configured to contact an outer surface of the inflatable balloon and move with the outer surface of the inflatable balloon as the inflatable balloon is inflated.

9. The drug delivery device of claim 8, wherein: the guide sleeve is configured to at least partially return to its original shape when the inflatable balloon is deflated.

10. The drug delivery device of any of the preceding claims, wherein: the inflatable balloon has a proximal taper, a middle cylindrical portion, and a distal taper.

11. The drug delivery device of claim 10 when dependent on claim 8 or 9, wherein: the distal portion of the guide cannula is configured to contact an outer surface of the proximal taper of the inflatable balloon.

12. The drug delivery device of any of the preceding claims, wherein: each guide sleeve includes a slit cut into one side of the guide sleeve.

13. The drug delivery device of any of the preceding claims, wherein: the guide sleeve is made of metal or alloy.

14. The drug delivery device of any of the preceding claims, wherein: a sheath movably disposed on the axially extending elongate member is also included.

15. The drug delivery device of claim 14, wherein: the sheath has an extended state in which the sheath covers the entirety of the two or more guide sleeves and at least a portion of the inflatable balloon, and a retracted state in which the sheath does not cover a portion of the inflatable balloon, optionally in which the sheath covers only a portion of the two or more guide sleeves.

16. The drug delivery device of any of the preceding claims, wherein: the needle is simultaneously reversibly retractable.

17. The drug delivery device of any one of claims 1-15, wherein: the needle is independently reversibly retractable.

18. The drug delivery device of claim 1, wherein: each of the needles includes a curved end portion, optionally each of the needles being configured to curve radially outwardly from the axially extending elongate member when the needle is extended from the guide cannula housing itself.

19. The drug delivery device of any of the preceding claims, wherein: the second lumen of the axially extending elongate member comprises two or more sub-lumens, each of the sub-lumens being in fluid connection with the lumen of the needle, optionally the two or more sub-lumens being not in fluid communication with each other.

20. The drug delivery device of any of the preceding claims, wherein: a support structure for positioning the guide sleeve and securing the guide sleeve to the axially extending elongate member is also included.

21. The drug delivery device of any of the preceding claims, wherein: the distal end of the axially extending elongate member is connected to a flexible tip.

22. The drug delivery device of any of the preceding claims, wherein: the drug delivery device is a rapid exchange catheter or a total exchange catheter.

23. The drug delivery device of any of the preceding claims, wherein: comprising at least one radiopaque element, optionally located within the balloon lumen, or on the axially extending elongate member, or on the guide cannula, and/or on the needle.

24. The drug delivery device of any of the preceding claims, wherein: a handle disposed at the proximal end of the axially extending elongate member is also included.

25. The drug delivery device of claim 24, wherein: the handle includes structure for controlling the maximum extension depth of the needle.

26. The drug delivery device of claim 24 or 25, wherein: the handle includes means for reversibly retracting the needle from the guide cannula.

27. The drug delivery device of claim 26, wherein: the device comprises first means for coarsely and reversibly retracting the needle and second means for finely and reversibly retracting the needle.

28. The drug delivery device of any one of claims 24 to 27, wherein: the handle includes a visual indicator that indicates the depth of extension of the needle.

29. The drug delivery device of any of the preceding claims, wherein: the guide sleeves comprise a curved portion at the distal end, optionally with the distal end of each guide sleeve being provided with an opening outwards from the catheter.

30. The drug delivery device of any of the preceding claims, wherein:

each of the needles includes a curved end;